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From 1994 and on, I have been doing research that
shows some of the diagnostic problems with the Fukuda
case definition. And remember, the Fukuda case
definition is the research case definition that has been
used throughout the world for the past 25 years. But
this Fukuda case definition identifies a heterogenous
group of patients, because core symptoms are not
required of all patients. So, as a consequence, samples
of patients with CFS based on Fukuda case definition
vary widely in different research groups and labs.
What is the impact of the case definitions on
prevalence rates?
In the late 1980s and early 1990s, the CDC conducted a
prevalence study where they started by asking
physicians in four cities to identify patients they thought
had CFS. At that time, a lot of physicians didn’t believe
CFS existed, so putting physicians as gatekeepers in the
selection of patients for this study resulted in a
prevalence rate that was very low. Also, many people in
the US do not have the financial resources to have a
physician, so relying on primary care doctors to identify
patients was another reason for low prevalence rates.
The study suggested that CFS was a rare disease that
affected fewer than 20,000 people in the US.
At that point, a group of researchers in Chicago began
working on a study that involved finding patients from a
random community sample, rather than a sample
referred from physicians. In 1995, with NIH funding, our
Chicago research team conducted a community-based
prevalence study, which found that about a million
people in the US had CFS. We also found that CFS
affected all ethnic and socioeconomic groups, and thus
we helped shatter the myth that CFS was a “Yuppie Flu”
disease.
What did William Reeves [then-head of the CDC
division in charge of the illness] do with the so-called
“empiric” criteria? And why did this increase the CDC’s
estimate of disease prevalence by a factor of 10?
In the early 2000s, Bill Reeves felt there was a need to
operationalize the Fukuda case definition. For example,
he tried to standardize the way we measure a patient’s
disability or a substantial reduction in functioning. He
used one instrument that has been referred to as the
SF-36. According to Reeves, if a patient met criteria for
one of several sub-scales within the SF-36, the patient
would meet the disability criteria for having CFS.
But one of these domains was “role emotional”
functioning. It turns out that every person with a major
depressive disorder meets the criteria for “role
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emotional” functioning. So you can’t just specify
instruments such as the SF-36; you have to specify
which sub-scales of the instruments you are going to
use, and what are the cut-off points. And if any of these
choices are wrong, you will identify people who have
another illness. My team gathered data on this point,
and we conducted a study that assessed people with
major depressive disorder, and found that over onethird
of them could be inappropriately classified as
having CFS under the so-called Reeves empiric criteria.
So, I think in the attempt to operationalize the Fukuda
criteria, Reeves made mistakes, and I believe that is one
of the reasons the estimated CDC prevalence estimates
increased ten-fold, from .24% in a 2003 sample to 2.54%
in 2007. They operationalized the Fukuda criteria in a
way that classified many people as having CFS when
they really had other illnesses.
At that time, many thought this increase in prevalence
figures that Reeves proposed was constructive as it
suggested that far more people had the illness, and thus
these findings could be used to argue for more
attention and funding due to this illness being so
widespread. But if you use a very broad criteria, and
bring into the illness case definition people who don’t
have the disease, then the entire research effort is
seriously compromised. Fortunately, over the past
decade, few researchers have used the Reeves way of
operationalizing CFS.
What about the CCC and ICC criteria?
The CCC case definition for ME/CFS in 2003 was better
because it specified key symptoms such as PEM. It was
developed as a clinical case definition, and now it’s
being used by several teams as a research case
definition. With the 2011 ME-ICC, I have noticed
problems, and in part this is due to them once again
requiring too many symptoms that could, as with the
Holmes criteria of 1988, bring into the ME category
some individuals who have a primary psychiatric
disorder. In addition, the ME-ICC criteria is complicated
to use, and many clinicians and scientists will have a
difficult time reliably using it with patients.
What is the problem you see with the IOM case
definition, apart from the name?
Well, it is true that Systemic Exertion Intolerance
Disease (SEID) is a name most patients dislike. However,
the IOM report was correct in requiring several core
symptoms, such as PEM. But I believe these authors
made a mistake in indicating that a patient could have
either cognitive impairment or orthostatic intolerance—
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